The objective of this research is to determine the natural history of monoclonal gammopathy of undetermined significance (MGUS). We will determine the prevalence of MGUS among Olmsted County, MN residents aged 50 years or greater (estimated population 26,022). We will obtain samples on most of the population in the course of their medical care. We will then contact the remaining residents by mail in an attempt to enroll them into the study as well. In order to ascertain the long-term outcome, we will also conduct a retrospective cohort study of survival and risk of multiple myeloma, macroglobulinemia, primary amyloidosis, and other plasma cell proliferative disorders in all cases of MGUS from the entire Southeastern Minnesota region (including Olmsted County) first diagnosed between January l, 1960 and December 31, 1997. We will follow the January l, 1998 survivors of the Southeastern Minnesota MGUS cohort including any asymptomatic prevalence cases and all subsequent newly diagnosed cases in a prospective study to assess predictors of outcome such as development of multiple myeloma or related disorders. The incidence of a variety of malignant and nonmalignant disorders will be determined in all MGUS patients in Southeastern Minnesota and a control cohort. Nurse abstractors will carefully review the Mayo Clinic records from 1960 through 1997 of all MGUS patients in Southeastern Minnesota for evidence of nonplasma cell neoplasms such as carcinoma or leukemia. Nonmalignant disorders consisting of hematologic diseases including pernicious anemia, idiopathic thrombocytopenic purpura, polycythemia vera, and myelodysplastic disorders will be evaluated as will connective tissue diseases including rheumatoid arthritis, lupus erythematosus, polymyalgia rheumatica, temporal arteritis, and ankylosing spondylitis. Neurologic disorders will include sensorimotor peripheral neuropathy, amyotrophic lateral sclerosis, and myesthenia gravis. Dermatologic diseases such as pyoderma grangrenosum, necrobiotic xanthogranuloma, lichen myxedematosus, Sezary syndrome, mycosis fungoides, and Kaposi's sarcoma will be sought. The presence of immunosuppression from HIV or transplants will be reviewed. Patients with liver disease, especially hepatitis C, will be included. This study will also provide bone marrow and peripheral blood for Projects II, III, IV, and V in an effort to better understand the biology of MGUS and multiple myeloma.